Esfandiari, Javanbakhsh (Stoney Brook, NY, US)

Plaque It! Sponsored by: Flash of Genius

11/172298

03/13/2007

06/30/2005

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Chembio Diagnostic Systems, Inc. (Medford, NY, US)

435/7.100

435/287.800, 435/287.100, 422/55, 435/4, 435/287.900, 435/287.200, 435/287.700, 436/501, 422/56, 422/58, 422/68.100, 435/288.700, 422/57, 435/288.300, 422/61

G01N15/06; B01L3/00; C12M1/34; C12M3/00; C12Q1/00; G01N21/00; G01N31/22; G01N33/53; G01N33/566

422/57, 436/501, 435/287.9, 435/7.1, 435/288.7, 422/68.1, 435/287.8, 422/58, 435/287.1, 435/288.3, 422/55, 435/287.2, 435/287.7, 422/56, 422/61, 435/4

3960488	Method and apparatus for quantitative surface inhibition test	June, 1976	Giaever
4041146	Method for detection of biological particles	August, 1977	Giaever
4042335	Integral element for analysis of liquids	August, 1977	Clement
4059405	Method and apparatus for analysis of constituent carried in fibrous medium	November, 1977	Sodickson et al.
4094647	Test device	June, 1978	Deutsch et al.
4144306	Element for analysis of liquids	March, 1979	Figueras
4235601	Test device and method for its use	November, 1980	Deutsch et al.
4323536	Multi-analyte test device	April, 1982	Columbus
4361537	Test device and method for its use	November, 1982	Deutsch et al.
4522786	Multilayered test device for detecting analytes in liquid test samples	June, 1985	Ebersole
4532107	Reagent test device	July, 1985	Siddigi
4588555	Device for use in chemical reactions and analyses	May, 1986	Provonchee
4595654	Method for detecting immune complexes in serum	June, 1986	Reckel et al.
4632901	Method and apparatus for immunoassays	December, 1986	Valkirs et al.
4668619	Multilayer homogeneous specific binding assay device	May, 1987	Greenquist et al.
4740468	Concentrating immunochemical test device and method	April, 1988	Weng et al.
4786595	Analytical element for analysis of an analyte	November, 1988	Arai et al.
4826759	Field assay for ligands	May, 1989	Guire et al.
4855240	Solid phase assay employing capillary flow	August, 1989	Rosenstein et al.
4857453	Immunoassay device	August, 1989	Ullman et al.
4870003	Simultaneous enzyme immunoassay for detecting antigen and/or antibody in humans	September, 1989	Kortright et al.
4886742	Enzyme immunoassay for detecting HIV antigens in human sera	December, 1989	Kortright et al.
4906439	Biological diagnostic device and method of use	March, 1990	Grenner
4912034	Immunoassay test device and method	March, 1990	Kalra et al.
4920046	Process, test device, and test kit for a rapid assay having a visible readout	April, 1990	McFarland et al.
4943522	Lateral flow, non-bibulous membrane assay protocols	July, 1990	Eisinger et al.
4956275	Migratory detection immunoassay	September, 1990	Zuk et al.
4956302	Lateral flow chromatographic binding assay device	September, 1990	Gordon et al.
4960691	Chromatographic test strip for determining ligands or receptors	October, 1990	Gordon et al.
4960710	Device and method of assaying for trace mounts of proteins	October, 1990	Lau
4981785	Apparatus and method for performing immunoassays	January, 1991	Nayak
4981786	Multiple port assay device	January, 1991	Dafforn et al.
5004584	Device for testing fluids	April, 1991	Rayman
5006464	Directed flow diagnostic device and method	April, 1991	Chu et al.
5006474	Bi-directional lateral chromatographic test device	April, 1991	Horstman et al.
5075077	Test card for performing assays	December, 1991	Durley, III et al.
5087556	Method for quantitative analysis of body fluid constituents	February, 1992	Ertinghausen
5091153	Chemical analysis test device	February, 1992	Bachand
5104793	Method for determining an analyte in a liquid sample using a zoned test device and an inhibitor for a label used in said method	April, 1992	Buck
5104811	Test carrier and method for the analytical determination of components of body fluids	April, 1992	Berger et al.
5110550	Test carrier for the analytical determination of a component of a liquid sample	May, 1992	Schlipfenbacher
5132208	Test carrier for the analysis of a sample liquid	July, 1992	Freitag et al.
5137808	Immunoassay device	August, 1992	Ullman et al.
5147780	Multiwell stat test	September, 1992	Pouletty et al.
5156952	Qualitative immunochromatographic method and device	October, 1992	Litman et al.
5162238	Test carrier for analysis of a liquid sample	November, 1992	Eikmeier et al.
5169789	Device and method for self contained solid phase immunodiffusion assay	December, 1992	Bernstein
5173433	Method for chemical analysis	December, 1992	Bachand
5200321	Microassay on a card	April, 1993	Kidwell
5202268	Multi-layered test card for the determination of substances in liquids	April, 1993	Kuhn et al.
5217905	Device and method for the rapid qualitative and quantitative determination of the presence of a reactive ligand in a fluid	June, 1993	Marchand et al.
5219762	Method and device for measuring a target substance in a liquid sample	June, 1993	Katamine et al.
5223436	Test carrier for the analytical determination of a component of a liquid sample	June, 1993	Freitag et al.
RE34312	Process and reagent for the determination of an antibody	July, 1993	Geiger et al.
5232835	Qualitative immunochromatographic method and device	August, 1993	Litman et al.
5238649	Specimen test unit	August, 1993	Nason
5240735	Method of manufacturing a test article for the determination of protein	August, 1993	Lau
5244631	Testing device	September, 1993	Morikawa
5244788	Method and apparatus for performing determinations of immune rectants in biological fluids	September, 1993	Hubscher
RE34405	Determination of analytes in particle-containing medium	October, 1993	Gould et al.
5275785	Test device for detecting an analyte in a liquid sample	January, 1994	May et al.
5281540	Test array for performing assays	January, 1994	Merkh et al.
5296192	Diagnostic test strip	March, 1994	Carroll et al.
5300439	Method, device, and composition for the assay of ions	April, 1994	Charlton
5306623	Visual blood glucose concentration test strip	April, 1994	Kiser et al.
5308775	Assay devices for concurrently detecting an analyte and confirming the test result	May, 1994	Donovan et al.
5332548	Analytical device and method of using same	July, 1994	Moore
5334502	Method of collecting, identifying, and quantifying saliva	August, 1994	Sangha
5338513	Test carrier for the analytical determination of a component of a liquid sample	August, 1994	Schlipfenbacher
5340748	Analyte-substitute reagent for use in specific binding assay methods, devices and kits	August, 1994	Baugher et al.
5356782	Analytical test apparatus with on board negative and positive control	October, 1994	Moorman et al.
5362654	Self-contained quantitative assay	November, 1994	Pouletty
5369007	Microassay on a card	November, 1994	Kidwell
5384264	Method and apparatus for single step assays of ligand-containing fluids	January, 1995	Chen et al.
5391478	Assay device and immunoassay	February, 1995	Greene et al.
5399316	Reaction vessel for conducting an immunological assay	March, 1995	Yamada
5411858	Manufacturing process for sample initiated assay device	May, 1995	McGeehan et al.
5418136	Devices for detection of an analyte based upon light interference	May, 1995	Miller et al.
5418142	Glucose test strip for whole blood	May, 1995	Kiser et al.
5418167	Rapid read-out biological indicator	May, 1995	Matner et al.
5424215	Assay for the determination of protein in a biological sample	June, 1995	Albarella et al.
5424220	Analysis element and method for determination of an analyte in a liquid sample	June, 1995	Goerlach-Graw et al.
5435970	Device for analysis for constituents in biological fluids	July, 1995	Mamenta et al.
5451504	Method and device for detecting the presence of analyte in a sample	September, 1995	Fitzpatrick et al.
5468648	Interrupted-flow assay device	November, 1995	Chandler
5470713	Method and element for measuring analytes in biological fluids using immobilized binder-analyte labeled complex	November, 1995	El Shami et al.
5474902	Semi-permeable capillary assay device	December, 1995	Uylen et al.
5482830	Devices and methods for detection of an analyte based upon light interference	January, 1996	Bogart et al.
5494830	Methods for performing determinations of immune reactants in biological fluids	February, 1996	Hubscher
5500350	Binding assay device	March, 1996	Baker et al.
5501985	Analyte-substitute reagent for use in specific binding assay methods, devices and kits	March, 1996	Baugher et al.
5514557	Method and kit for detecting antibodies specific for HLA and/or platelet glycoproteins	May, 1996	Moghaddam
5521102	Controlled sensitivity immunochromatographic assay	May, 1996	Boehringer et al.
5532133	Plasmodium vivax blood stage antigens, PvESP-1, antibodies, and diagnostic assays	July, 1996	Barnwell
5541057	Methods for detection of an analyte	July, 1996	Bogart et al.
5550063	Methods for production of an optical assay device	August, 1996	Bogart
5552272	Detection of an analyte by fluorescence using a thin film optical device	September, 1996	Bogart
5558834	Device and method of seperating and assaying whole blood	September, 1996	Chu et al.
5559041	Immunoassay devices and materials	September, 1996	Kang et al.
5567594	Methods and compositions for the detection and treatment of diseases associated with antigens of microorganisms	October, 1996	Calenoff
5571667	Elongated membrane flow-through diagnostic device and method	November, 1996	Chu et al.
5591645	Solid phase chromatographic immunoassay	January, 1997	Rosenstein
5602040	Assays	February, 1997	May et al.
5604110	Binding assay device	February, 1997	Baker et al.
5607863	Barrier-controlled assay device	March, 1997	Chandler
5616467	Method and kit for analyte detection employing gold-sol bound antibodies	April, 1997	Olsen et al.
5620845	Immunoassay diagnostic kit	April, 1997	Gould et al.
5622871	Capillary immunoassay and device therefor comprising mobilizable particulate labelled reagents	April, 1997	May et al.
5624809	Device for immunochromatographic analysis	April, 1997	Skold et al.
5629164	Enzyme immunoassay device	May, 1997	Rivers
5629214	Methods for forming an optical device for detecting the presence or amount of an analyte	May, 1997	Crosby
5639671	Methods for optimizing of an optical assay device	June, 1997	Bogart et al.
5641639	Binding assay device	June, 1997	Perry
5648274	Competitive immunoassay device	July, 1997	Chandler
5656503	Test device for detecting analytes in biological samples	August, 1997	May et al.
5658801	Medical test kit	August, 1997	Poissant et al.
5670381	Devices for performing ion-capture binding assays	September, 1997	Jou et al.
5686315	Assay device for one step detection of analyte	November, 1997	Pronovost
5695928	Rapid immunoassay for detection of antibodies or antigens incorporating simultaneous sample extraction and immunogenic reaction	December, 1997	Stewart
5695930	HIV test kit method for detecting anti-HIV-I antibodies in saliva	December, 1997	Weinstein et al.
5710005	Analyte detection with a gradient lateral flow device	January, 1998	Rittenburg
5714341	Saliva assay method and device	February, 1998	Thieme et al.
5714389	Test device and method for colored particle immunoassay	February, 1998	Charlton et al.
5723345	Method and device for specific binding assay	March, 1998	Yamauchi et al.
5726010	Reversible flow chromatographic binding assay	March, 1998	Clark
5728587	Immunoassay devices and materials	March, 1998	Kang et al.
5739041	Diagnostic detection device	April, 1998	Nazareth et al.
5750333	Reversible flow chromatographic binding assay	May, 1998	Clark
5766961	One-step lateral flow nonbibulous assay	June, 1998	Pawlak et al.
5766962	Device for collecting and testing samples	June, 1998	Childs et al.
5770460	One-step lateral flow nonbibulous assay	June, 1998	Pawlak et al.
5773234	Method and device for chlamydia detection	June, 1998	Pronovost et al.
5786220	Assays and devices for distinguishing between normal and abnormal pregnancy	July, 1998	Pronovost et al.
5807756	Ceramic assembly for use in biological assays	September, 1998	Bauman et al.
5814522	Multilayer analytical element for the determination of an analyte in a liquid	September, 1998	Zimmer et al.
5824268	Rapid self-contained assay format	October, 1998	Bernstein et al.
5827646	Diagnostic reagents for the detection of antibodies to EBV	October, 1998	Middeldorp et al.
5846838	Opposable-element assay device employing conductive barrier	December, 1998	Chandler
5853670	Liquid transfer device for controlling liquid flow	December, 1998	Bunce	422/100
5861265	Binding assay method using a signal preventing reagent	January, 1999	Perry
5869272	Methods for detection of gram negative bacteria	February, 1999	Bogart et al.
5869345	Opposable-element assay device employing conductive barrier	February, 1999	Chandler
5872713	Synchronized analyte testing system	February, 1999	Douglas et al.
5874216	Indirect label assay device for detecting small molecules and method of use thereof	February, 1999	Mapes
5877028	Immunochromatographic assay device	March, 1999	Chandler et al.
5879951	Opposable-element assay device employing unidirectional flow	March, 1999	Sy
5885526	Analytical device for membrane-based assays	March, 1999	Chu
5885527	Diagnostic devices and apparatus for the controlled movement of reagents without membrances	March, 1999	Buechler
5891650	Kinase receptor activation assay	April, 1999	Godowski et al.
5900379	Analytical device	May, 1999	Noda et al.
5902722	Method of detecting organisms in a sample	May, 1999	Di Cesare et al.
5912116	Methods of measuring analytes with barrier webs	June, 1999	Caldwell
5922533	Rapid assay for simultaneous detection and differentiation of antibodies to HIV groups	July, 1999	Vallari et al.
5922615	Assay devices comprising a porous capture membrane in fluid-withdrawing contact with a nonabsorbent capillary network	July, 1999	Nowakowski et al.
5939252	Detachable-element assay device	August, 1999	Lennon et al.
5939272	Non-competitive threshold ligand-receptor assays	August, 1999	Buechler et al.
5948695	Device for determination of an analyte in a body fluid	September, 1999	Douglas et al.
5955377	Methods and kits for the amplification of thin film based assays	September, 1999	Maul et al.
5958790	Solid phase transverse diffusion assay	September, 1999	Cerny
5965458	Test strip, its production and use	October, 1999	Kouvonen et al.
5972720	Stabilization of metal conjugates	October, 1999	Nichtl et al.
5976895	Device for the collection, testing and shipment of body fluid samples	November, 1999	Cipkowski
5985675	Test device for detection of an analyte	November, 1999	Charm et al.
5989921	Test device and method for colored particle immunoassay	November, 1999	Charlton et al.
5998220	Opposable-element assay devices, kits, and methods employing them	December, 1999	Chandler
5998221	Non-instrumented assay with quantitative and qualitative results	December, 1999	Malick et al.
6008056	Sample volume control for lateral flow chromatography	December, 1999	Thieme
6017767	Assay device	January, 2000	Chandler
6027890	Methods and compositions for enhancing sensitivity in the analysis of biological-based assays	February, 2000	Ness et al.
6040195	Diagnostic sanitary test strip	March, 2000	Carroll et al.
6046013	Process for identifying specific antibodies associated with HLA	April, 2000	Tidey et al.
6046057	Analyte assaying device	April, 2000	Nazareth et al.
6057166	Fecal test method	May, 2000	Childs et al.
6060326	Method to detect canine IgE and kit therefor	May, 2000	Frank et al.
6063337	Test strip for measuring device for optically detecting the concentration of a substance in a body fluid	May, 2000	Markart
6087184	Opposable-element chromatographic assay device for detection of analytes	July, 2000	Magginetti et al.
6106732	Integral blood plasma or serum isolation, metering and transport device	August, 2000	Johnston et al.
6140134	Analyte detection with a gradient lateral flow device	October, 2000	Rittenburg
6140136	Analytical test device and method of use	October, 2000	Lee
6168956	Multiple component chromatographic assay device	January, 2001	Chandler
6187268	Transparent flow through membrane for dry reagent analytical devices	February, 2001	Albarella et al.
6187598	Capillary immunoassay and device therefor comprising mobilizable particulate labelled reagents	February, 2001	May et al.
6194220	Non-instrumented assay with quantitative and qualitative results	February, 2001	Malick et al.
6197494	Apparatus for performing assays on liquid samples accurately, rapidly and simply	March, 2001	Oberhardt
6221625	Enzyme-labeled immunoassay and device therefor	April, 2001	Ashihara et al.
6221678	Apparatus and method for analyte detection	April, 2001	Chandler
6224831	Microassay device and methods	May, 2001	Stafford et al.
6228660	Capillary immunoassay and device therefor comprising mobilizable particulate labelled reagents	May, 2001	May et al.
6235464	Immunoassay on a preblocked solid surface	May, 2001	Henderson et al.
6248598	Immunoassay that provides for both collection of saliva and assay of saliva for one or more analytes with visual readout	June, 2001	Bogema
6258548	Single or multiple analyte semi-quantitative/quantitative rapid diagnostic lateral flow test system for large molecules	July, 2001	Buck
6271040	Diagnostic devices method and apparatus for the controlled movement of reagents without membranes	August, 2001	Buechler
6271045	Device for determination of an analyte in a body fluid	August, 2001	Douglas et al.
6271046	Apparatus and method for analyte detection	August, 2001	Chandler
6277650	Analyte assaying device	August, 2001	Nazareth et al.
6284550	Diagnostic sanitary test strip	September, 2001	Carroll et al.
6287875	Internally referenced competitive assays	September, 2001	Geisberg
6297020	Device for carrying out lateral-flow assays involving more than one analyte	October, 2001	Brock
6297060	Assay devices comprising a porous capture membrane in fluid-withdrawing contact with a nonabsorbent capillary network	October, 2001	Nowakowski et al.
6300142	Device and apparatus for conducting an assay	October, 2001	Andrewes et al.
RE37437	Sheet-like diagnostic device	November, 2001	Friesen et al.
6316205	Assay devices and methods of analyte detection	November, 2001	Guan et al.
6316264	Test strip for the assay of an analyte in a liquid sample	November, 2001	Corey et al.
6319676	Diagnostic detection device and method	November, 2001	Nazareth et al.
6326214	Immunity testing device	December, 2001	Liu et al.
6335205	Method and test strip for determining an analyte	January, 2002	Bausback
6352862	Analytical test device for imuno assays and methods of using same	March, 2002	Davis et al.
6362008	Generic signalling mechanism for detection of analytes	March, 2002	Kohn et al.
6368875	Internally referenced competitive assays	April, 2002	Geisberg
6368876	One step immunochromatographic device and method of use	April, 2002	Huang et al.	436/518
6372514	Even fluid front for liquid sample on test strip device	April, 2002	Lee
6372515	Device for the testing of fluid samples and process for making the device	April, 2002	Casterlin et al.
6372516	Lateral flow test device	April, 2002	Sun
6376195	Indirect label assay device for detecting small molecules and method of use thereof	April, 2002	Mapes
6399398	Assay device	June, 2002	Cunningham et al.
6403383	Diagnostic test kit for immunological assays of fluid samples	June, 2002	Casterlin et al.
6403384	Device and method for analyzing a biologic sample	June, 2002	Lea
6406922	Device for the testing of body fluid samples	June, 2002	Casterlin et al.
6413473	Multicomponent test systems useful in analyzing liquid samples, and uses therefor	July, 2002	Bacon
6413784	Multi-sectioned fluid delivery devices for detecting target molecules by immunoassay	July, 2002	Lundsgaard et al.
6436722	Device and method for integrated diagnostics with multiple independent flow paths	August, 2002	Clark et al.
6455324	Embossed test strip system	September, 2002	Douglas
6472226	Assay using porosity-reduction to inhibit migration	October, 2002	Barradine et al.
6475805	Method for detection of an analyte	November, 2002	Charm et al.
6485982	Test device and method for colored particle immunoassay	November, 2002	Charlton
6489129	Antigen-specific IgM detection	December, 2002	Faatz et al.
6492127	Lateral flow testing device with on-board chemical reactant	December, 2002	Goodell et al.
6500629	Materials and methods for detection and quantitation of an analyte	December, 2002	Cleaver et al.
6503702	Rapid immunoassay for detection of antibodies or antigens incorporating simultaneous sample extraction and immunogenic reaction	January, 2003	Stewart
6503722	Diagnostic tests and kits for Clostridium difficile	January, 2003	Valkirs
6511814	Method and device for detecting analytes in fluids	January, 2003	Carpenter
6514769	Multiple analyte assay device with sample integrity monitoring system	February, 2003	Lee
6514773	Method of detecting surface contamination by an analyte	February, 2003	Klein et al.
6528321	Opposable-element chromatographic assay device for detection of analytes in whole blood samples	March, 2003	Fitzgerald et al.
6528322	Analytical method and apparatus	March, 2003	Carlsson et al.
6528323	Bidirectional lateral flow test strip and method	March, 2003	Thayer et al.
6528325	Method for the visual detection of specific antibodies in human serum by the use of lateral flow assays	March, 2003	Hubscher et al.
6534324	Rapid assay strip and method of rapid competitive assay	March, 2003	Zin
6544474	Device for determination of an analyte in a body fluid using small sample sizes	April, 2003	Douglas
6548309	Procedure for assay of liquids containing undissolved solids, semisolids or colloids	April, 2003	Moore et al.
6551842	Method and device for detecting analytes in fluids	April, 2003	Carpenter
6592815	Analytical test element with a narrowed capillary channel	July, 2003	Zimmer
6593085	Assay method and apparatus	July, 2003	Barnett et al.
6602719	Method and device for detecting analytes in fluids	August, 2003	Carpenter
6617116	Assay devices and methods of analyte detection	September, 2003	Guan et al.
6623955	Rapid read-out biological indicator	September, 2003	Matner et al.
6627459	Immunoassay controls	September, 2003	Tung et al.
6632681	Reagent delivery device and method of use	October, 2003	Chu
6645732	Antigen-specific IgG detection	November, 2003	Faatz et al.
6649418	Internally referenced competitive assays	November, 2003	Geisberg
6656744	One-step lateral flow assays	December, 2003	Pronovost et al.
6656745	Devices and methods for a multi-level, semi-quantitative immunodiffusion assay	December, 2003	Cole
6660469	Apparatus and method testing a biological fluid	December, 2003	Wright et al.
6663833	Integrated assay device and methods of production and use	December, 2003	Stave et al.
6673628	Analytical test device and method	January, 2004	Freitag et al.
RE38430	Solid phase chromatographic immunoassay	February, 2004	Rosenstein
6686167	Test device for detecting semen and method of use	February, 2004	Bagaria
6699722	Positive detection lateral-flow apparatus and method for small and large analytes	March, 2004	Bauer et al.
6703196	General purpose structure of an analytical element and its application for analyte determination	March, 2004	Klepp et al.
6706539	Enzyme substrate delivery and product registration in one step enzyme immunoassays	March, 2004	Nelson et al.
6713309	Microarrays and their manufacture	March, 2004	Anderson et al.
6727073	Method for detecting enteric disease	April, 2004	Moore et al.
6737277	Immunoassay devices and materials	May, 2004	Kang et al.
6750031	Displacement assay on a porous membrane	June, 2004	Ligler et al.
6753190	Immunologic test method and immunologic test kit	June, 2004	Okada et al.
6767710	Prewetting stop flow test strip	July, 2004	DiNello et al.
6767714	Diagnostic detection device and method	July, 2004	Nazareth et al.
6780651	Device for determination of an analyte in a body fluid	August, 2004	Douglas et al.
6790611	Assay for directly detecting a RS virus related biological cell in a body fluid sample	September, 2004	Lassen et al.
6797481	Simultaneous screening of multiple analytes	September, 2004	Ullman et al.
6808889	Method and device for detection of Apo A, Apo B and the ratio thereof in saliva	October, 2004	Fitzpatrick et al.
6808937	Displacement assay on a porous membrane	October, 2004	Ligler et al.
6812038	Assay device and use thereof	November, 2004	Mendel-Hartvig et al.
6818180	Devices for testing for the presence and/or concentration of an analyte in a body fluid	November, 2004	Douglas et al.
6818455	Capillary immunoassay and device therefor comprising mobilizable particulate labelled reagents	November, 2004	May et al.
6824975	Incorporation of selective binding substances in a solid phase assay device	November, 2004	Hubscher et al.
6824997	Process and materials for the rapid detection of streptococcus pneumoniae employing purified antigen-specific antibodies	November, 2004	Moore et al.
6828110	Assays for detection of Bacillus anthracis	December, 2004	Lee et al.
RE38688	Sheet-like diagnostic device	January, 2005	Friesen et al.
6844200	Device for carrying out lateral-flow assays involving more than one analyte	January, 2005	Brock
6846635	Microarrays and their manufacture	January, 2005	Anderson et al.
6849414	Assay devices and methods of analyte detection	February, 2005	Guan et al.
6855561	Method for adding an apparent non-signal line to a lateral flow assay	February, 2005	Jerome et al.
6863866	Self-contained devices for detecting biological contaminants	March, 2005	Kelly et al.
6867051	Point of care diagnostic systems	March, 2005	Anderson et al.
6887701	Microarrays and their manufacture	May, 2005	Anderson et al.
6905835	Assay for anti transglutaminase antibodies detection useful in celicac disease diagnosis	June, 2005	Sorell Gomez et al.
6924153	Quantitative lateral flow assays and devices	August, 2005	Boehringer et al.
6927068	Rapid and non-invasive method to evaluate immunization status of a patient	August, 2005	Simonson et al.
6991940	Diagnostic sanitary test strip	January, 2006	Carroll et al.
7018847	Assay device with timer function	March, 2006	Mendel-Hartvig et al.
7045342	Diagnostic detection device and method	May, 2006	Nazareth et al.
7049130	Diagnostic sanitary test strip	May, 2006	Carroll et al.
7109042	Assays	September, 2006	May et al.	436/514
20010012637	Device for the testing of body fluid samples	August, 2001	Casterlin et al.
20010026942	Detection of contaminants using self-contained devices employing target material binding dyes	October, 2001	Carpenter et al.
20010026944	Immunoassay system	October, 2001	Chung et al.
20010034068	Screening device and methods of screening immunoassay tests and agglutination tests	October, 2001	Spivey et al.
20010039057	Devices for testing for the presence and/or concentration of an analyte in a body fluid	November, 2001	Douglas et al.
20010048893	DIAGNOSTIC ASSAY DEVICE	December, 2001	Norris et al.
20020001853	DETECTION OF VERY LOW QUANTITIES OF ANALYTE BOUND TO A SOLID PHASE	January, 2002	Obremski et al.
20020015663	ORAL COLLECTION DEVICE AND KIT	February, 2002	Goldstein et al.
20020019062	Assay devices	February, 2002	Lea et al.
20020031839	METHOD AND APPARATUS FOR RAPID ANALYSIS OF ANALYTES IN BIOLOGICAL SAMPLES	March, 2002	McNeirney et al.
20020046614	Apparatus for sampling and testing a specimen	April, 2002	Alley
20020048819	Test strip for use in an apparatus for sampling and testing a specimen	April, 2002	Alley
20020052050	Device for determination of an analyte a in body fluid	May, 2002	Douglas et al.
20020057991	Self-contained devices for detecting biological contaminants	May, 2002	Kelly et al.
20020058330	Diagnostic sanitary test strip	May, 2002	Carroll et al.
20020110803	Highly cost-effective analytical device for performing immunoassays with ultra high sensitivity	August, 2002	Dhar et al.
20020119497	Binding assays	August, 2002	Wild et al.
20020142291	Positive detection lateral-flow apparatus and method for small and large analytes	October, 2002	Bauer et al.
20020155028	Lateral flow contact test apparatus	October, 2002	Wong
20020173050	Prewetting stop flow test strip	November, 2002	DiNello et al.
20020192839	Collection device for single step assay of oral fluids	December, 2002	Mink et al.	436/514
20030045001	Immunochromatographic test strip with arcuate sample application zone for ease-of-use in the field	March, 2003	Burgess et al.
20030118480	Diagnostic device, system and method	June, 2003	Kaylor et al.
20030124740	Binding assay device with non-absorbent carrier material	July, 2003	Bachand
20030138351	DISPOSABLE DEVICES FOR TESTING BODY FLUIDS	July, 2003	Etes et al.
20030143639	Analyzing device	July, 2003	Matsushita et al.	435/7.9
20030180967	Immunoassay method, test strip for use therein, and immunoassay apparatus	September, 2003	Shigetoh
20040087036	Immunoassay system	May, 2004	Chung et al.
20040142495	Analyte detecting article and method	July, 2004	Hartman et al.
20040161859	Lateral flow immunoassay controls	August, 2004	Guo et al.
20040184954	Lateral flow immunoassay devices for testing saliva and other liquid samples and methods of use of same	September, 2004	Guo et al.
20040219694	Lateral flow test format for enzyme assays	November, 2004	Chittock et al.
20040235189	Reversed chromatographic immunoassay	November, 2004	Lu
20040241779	Dry chemistry, lateral flow-reconstituted chromatographic enzyme-driven assays	December, 2004	Piasio et al.
20040248322	Diagnostic test for analytes in a sample	December, 2004	Charlton
20050074900	Microfluidic flow-through immunoassay for simultaneous detection of multiple proteins in a biological sample	April, 2005	Morgan et al.
20050079629	Lateral flow assay devices and methods of use	April, 2005	Guo et al.
20050112779	Extension of the dynamic detection range of assay devices	May, 2005	Wei et al.
20050112780	Method for extending the dynamic detection range of assay devices	May, 2005	Song
20050112782	Diagnostic devices and apparatus for the controlled movement of reagents without membranes	May, 2005	Buechler
20050130293	Dry reagent strip configuration, composition and method for multiple analyte determination	June, 2005	Blatt et al.
20050130319	Molecular binding event detection using separation channels	June, 2005	Blegelsen et al.
20050136500	Flow-through assay devices	June, 2005	Yang et al.
20050142032	Test system for determining an analyte in a liquid sample	June, 2005	Hoenes et al.
20050164404	Diagnostic testing process	July, 2005	Marlborugh et al.
20050170527	Quantitative lateral flow assays and devices	August, 2005	Boehringer et al.
20050208677	Lateral flow test strip	September, 2005	Owens et al.
20050227371	Hybrid phase lateral flow assay	October, 2005	Gokhan
20050244985	Chromatographic Assay Device and Methods	November, 2005	Freitag et al.
20050244986	Assays	November, 2005	May et al.
20060099719	Biochemical assay	May, 2006	Curcio
20060121626	Diagnostic assay device	June, 2006	Imrich
20060134803	Immunoassay devices and use thereof	June, 2006	Esfandiari

Le, Long V.

Diramio, Jacqueline A.

Gordon & Jacobson, PC

This application claims priority from provisional application 60/680,884 filed May 13, 2005 and from provisional application 60/660,695 filed Mar. 11, 2005, which are hereby incorporated by reference herein in their entireties.

What is claimed is:

1. A test device for use with a solution and for use with a conjugate having a marker, the test device for determining the presence of a ligand in a liquid sample, the test device comprising: a) a first sorbent strip having a first length and a first width, said first length being substantially larger than said first width, and having a first location for receiving the solution and defining a first migration path for the solution and the conjugate; b) a second sorbent strip having a second length and a second width, said second length being substantially larger than said second width, said second sorbent strip distinct from said first sorbent strip having a second location for receiving the liquid sample and defining a second migration path for the sample distinct from said first migration path; and c) a test site located on or in at least one of said first sorbent strip or said second sorbent strip, said test site having an immobilized ligand-binding mechanism, said first and second sorbent strips touching each other at the test site, and said second migration path extending laterally from said second location to at least said test site such that application of the liquid sample to the second location requires time for the liquid sample to laterally flow to the test site and does not immediately wet the test site upon application.

2. A test device according to claim 1, further comprising: d) a housing defining a first opening adjacent said first location, a second opening adjacent said second location, and a window adjacent said test site through which said test site is viewable.

3. A test device according to claim 1, further comprising: said conjugate, wherein said first sorbent strip supports said conjugate.

4. A test device according to claim 3, wherein: said ligand-binding mechanism is an antigen or antibody for said ligand, and said conjugate comprises an antigen or antibody for the ligand and said marker coupled to the antigen or antibody.

5. A test device according to claim 4, wherein: said marker is a colored marker viewable in the visible spectrum.

6. A test device according to claim 2, wherein: one or both of said first and second sorbent strips includes a control site, and said housing defines a window for viewing said control site.

7. A test device according to claim 1, wherein: said first sorbent strip and said second sorbent strip are arranged in a “T” configuration.

8. A test device according to claim 1, wherein: said first sorbent strip and second sorbent strip are arranged in a “+” configuration.

9. A test device according to claim 1, wherein: said first sorbent strip has a first pore size and said second sorbent strip has a second pore size.

10. A test device according to claim 9, wherein: said second pore size is larger than said first pore size.

11. A test device according to claim 10, wherein: said first pore size is between 3 and 20 microns, and said second pore size is between 20 and 40 microns.

12. A test device according to claim 2, wherein: one or both of said first and second sorbent strips includes a control site, and either said window is sized to permit viewing of said control site or a second window is provided in said housing to permit viewing of said control site.

13. A test device according to claim 1, further comprising: said solution, wherein said solution comprises a buffer.

14. A test device according to claim 1, further comprising: said solution, wherein said solution comprises a subsystem of a buffer and a conjugate having an antigen or antibody for the ligand and a marker coupled to the antigen or antibody.

15. A test device according to claim 1, wherein: said immobilized ligand-binding mechanism comprises an HIV antigen or antibody.

16. A test device according to claim 1, wherein: said immobilized ligand-binding mechanism comprises antigens, antibodies, aptamers, nucleic acids, or enzymes for testing for at least one of pregnancy, HIV, tuberculosis (TB), prion, urine-analysis/drug, Chlamydia, cardiac markers, cancer markers, Chagas, dental bacteria (SM/LC), strep A, influenza A, influenza B, adenovirus/rotavirus, CPV, FIV, FeLV, and heartworm.

17. A test device according to claim 1, wherein: said first sorbent strip includes a first membrane and a first backing and said second sorbent strip includes a second membrane and a second backing, and said first sorbent strip and said second sorbent strip are arranged such that said first membrane is in contact with said second membrane.

18. A test device according to claim 17, further comprising: a first adhesive backing card underlying or overlying said first sorbent strip.

19. A test device according to claim 18, further comprising: a second adhesive backing card underlying or overlying said second sorbent strip.

20. A test device according to claim 1, wherein: said first sorbent strip and said second sorbent strip include a single membrane integral to both of said first sorbent strip and said second sorbent strip.

21. A test device according to claim 1, wherein: said test device is for determining the presence of a plurality of different ligands in the liquid sample, and said test site has a plurality of separate immobilized ligand-binding mechanisms for separately binding to respective of said plurality of different ligands.

22. A test device according to claim 21, wherein: said plurality of separate immobilized ligand-binding mechanisms includes a tuberculosis antigen and at least one HIV antigen.

23. A test device according to claim 21, wherein: said plurality of separate immobilized ligand-binding mechanisms includes p24 antibodies and at least one of an HIV1 and an HIV2 antigen.

24. A test device according to claim 21, wherein: said first sorbent strip supports a plurality of different conjugates comprising antigens and/or antibodies for the plurality of different ligands and markers coupled to the antigens and/or antibodies.

25. A test device for use with a solution and for use with a conjugate having a marker, the test device for determining the presence of a ligand in a liquid sample, the test device comprising: a) a first sorbent strip having a first length and a first width, said first length being substantially larger than said first width, and having a first location for receiving a solution and defining a first migration path for the solution and the conjugate; b) a second sorbent strip having a second length and a second width, said second length being substantially larger than said second width, said second sorbent strip distinct from said first sorbent strip having a second location for receiving the liquid sample and defining a second migration path for the sample distinct from said first migration path; and c) a test site located on or in at least one of said first or second sorbent strips, said test site having a test line containing an immobilized ligand-binding mechanism deposited on or in the at least one of said first or second sorbent strips, said first and second sorbent strips in direct contact with each other at the test line and said second migration path extending laterally from said second location to at least said test site such that application of the liquid sample to the second location requires time for the liquid sample to laterally flow to the test site and does not immediately wet the test site upon application.

26. A test device for use with a solution and for use with a conjugate having a marker, the test device for determining the presence of a ligand in a liquid sample, the test device comprising: a) a first sorbent nitrocellulose strip of a first pore size and having a first length and a first width, said first length being substantially larger than said first width, and having a first location for receiving the solution and defining a first migration path for the solution and the conjugate; b) a second sorbent nitrocellulose strip distinct from said first sorbent strip having a second pore size larger than said first pore size and a second length and a second width, said second length being substantially larger than said second width, and having a second location for receiving the liquid sample and defining a second migration path for the sample distinct from said first migration path; and c) a test site located on or in at least one of said first sorbent strip or said second sorbent strip, said test site having an immobilized ligand-binding mechanism, and said first and second sorbent nitrocellulose strips touching each other at the test site, whereby the liquid sample, after being received at the second location migrates does not immediately wet said test site, but laterally over time on said second migration path to said test site and thereafter, migration of the liquid sample on said first migration path is relatively limited due to said first pore size being smaller than said second pore size.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates broadly to immunoassay devices and the methods for their use. More particularly, this invention relates to chromatographic rapid test strips for detection of a ligand in a body fluid.

2. State of the Art

Many types of ligand-receptor assays have been used to detect the presence of various substances, often generally called ligands, in body fluids such as blood, urine, or saliva. These assays involve antigen antibody reactions, synthetic conjugates comprising radioactive, enzymatic, fluorescent, or visually observable polystyrene or metal sol tags, and specially designed reactor chambers. In all these assays, there is a receptor, e.g., an antibody, which is specific for the selected ligand or antigen, and a means for detecting the presence, and in some cases the amount, of the ligand-receptor reaction product. Some tests are designed to make a quantitative determination, but in many circumstances all that is required is a positive/negative qualitative indication. Examples of such qualitative assays include blood typing, most types of urinalysis, pregnancy tests, and AIDS tests. For these tests, a visually observable indicator such as the presence of agglutination or a color change is preferred.

Even the qualitative assays must be very sensitive because of the often small concentration of the ligand of interest in the test fluid. False positives can also be troublesome, particularly with agglutination and other rapid detection methods such as dipstick and color change tests. Because of these problems, so-called “sandwich” assays and other sensitive detection mechanisms which use metal sols or other types of colored particles have been developed.

In a “sandwich” assay, a target analyte such as an antigen is “sandwiched” between a labeled antibody and an antibody immobilized onto a solid support. The assay is read by observing the presence and/or amount of bound antigen-labeled antibody complex. In a “competition” immunoassay, antibody bound to a solid surface is contacted with a sample containing an unknown quantity of antigen analyte and with labeled antigen of the same type. The amount of labeled antigen bound on the solid surface is then determined to provide an indirect measure of the amount of antigen analyte in the sample.

Because these and other assays can detect both antibodies and antigens, they are generally referred to as immunochemical ligand-receptor assays or simply immunoassays.

Solid phase immunoassay devices, whether of the sandwich or competition type, provide sensitive detection of an analyte in a biological fluid sample such as blood, urine, or saliva. Solid phase immunoassay devices incorporate a solid support to which one member of a ligand-receptor pair, usually an antibody, antigen, or hapten, is bound. Common early forms of solid supports were plates, tubes, or beads of polystyrene which were well known from the fields of radioimmunoassay and enzyme immunoassay. In the last decade, a number of porous materials such as nylon, nitrocellulose, cellulose acetate, glass fibers, and other porous polymers have been employed as solid supports.

A number of self-contained immunoassay kits using porous materials as solid phase carriers of immunochemical components such as antigens, haptens, or antibodies have been described. These kits are usually dipstick, flow-through, or migratory in design.

In the more common forms of dipstick assays, as typified by home pregnancy and ovulation detection kits, immunochemical components such as antibodies are bound to a solid phase. The assay device is “dipped” for incubation into a sample suspected of containing unknown antigen analyte. Enzyme-labeled antibody is then added, either simultaneously or after an incubation period. The device is then washed and inserted into a second solution containing a substrate for the enzyme. The enzyme-label, if present, interacts with the substrate, causing the formation of colored products which either deposit as a precipitate onto the solid phase or produce a visible color change in the substrate solution.

Flow-through type immunoassay devices were designed to obviate the need for extensive incubation and cumbersome washing steps associated with dipstick assays. Valkirs et al., U.S. Pat. No. 4,632,901, disclose a device comprising antibody (specific to a target antigen analyte) bound to a porous membrane or filter to which is added a liquid sample. As the liquid flows through the membrane, target analyte binds to the antibody. The addition of sample is followed by addition of labeled antibody. The visual detection of labeled antibody provides an indication of the presence of target antigen analyte in the sample.

Korom et al., EP-A 0 299 359, discloses a variation in the flow-through device in which the labeled antibody is incorporated into a membrane which acts as a reagent delivery system.

The requirement of multiple addition and washing steps with dipstick and flow-through type immunoassay devices increases the likelihood that minimally trained personnel and home users will obtain erroneous assay results.

In migration type assays, a membrane is impregnated with the reagents needed to perform the assay. An analyte detection zone is provided in which labeled analyte is bound and assay indicia is read. See, for example, Tom et al., U.S. Pat. No. 4,366,241, and Zuk, et al. U.S. Pat. No. 4,596,275. The sensitivity of migration type assays is frequently reduced, however, by the presence or formation in the sample of undesirable solid components which block the passage of labeled analyte to the detection zone. Assay sensitivity also declines when migration assay devices are flooded with too much liquid sample.

Migration assay devices usually incorporate within them reagents which have been attached to colored labels (i.e., conjugates), thereby permitting visible detection of the assay results without addition of further substances. See, for example, Bernstein, U.S. Pat. No. 4,770,853. Among such labels are gold sol particles such as those described by Leuvering in U.S. Pat. No. 4,313,734, dye sol particles such as described in U.S. Pat. No. 4,373,932 by Gribnau et al., dyed latex such as described by May et al., WO 88/08534, and dyes encapsulated in liposomes by Campbell et al., U.S. Pat. No. 4,703,017. These colored labels are generally limited in terms of the immobilization methods which are suitable. Moreover, they require a relatively large amount of ligand molecule and can involve expensive reagents, thereby adding to the cost. Thus, there still remains a need for extremely reliable but inexpensive rapid detection devices. There also still remains a need for a highly sensitive assay which can utilize a small sample volume while providing accurate results.

SUMMARY OF THE INVENTION

It is therefore an object of the invention to provide a rapid detection immunoassay device.

It is another object of the invention to provide immunoassay devices which are simple to use and provide accurate results.

It is a further object of the invention to provide immunoassay devices which do not require migration of analytes along the same path as conjugate carrying buffer solutions.

It is also an object of the invention to provide rapid detection immunoassay devices which are simple in construction.

It is an additional object of the invention to provide immunoassay devices which can use either a dry or liquid conjugate system.

Another object of the invention is to provide a highly sensitive immunoassay device which provides accurate results while using small sample volumes.

A further object of the invention is to provide highly sensitive immunoassay devices which are useful with different types of body fluids.

In accord with these objects, which will be discussed in detail below, both dry and liquid conjugate immunoassay device systems are provided. The systems of the invention include test cells with a first sorbent material having a first location for receiving a buffer solution (in the case of a dry conjugate system) or a conjugate solution (in the case of a liquid conjugate system) with the first sorbent material defining a first horizontal flow path, a second sorbent material having a second location for receiving a sample with the second sorbent material defining a second horizontal flow path distinct from the first flow path, and a test line or test site with immobilized antigens or antibodies or other ligand binding molecules such as aptamers, nucleic acids, etc. located in a test zone at a junction of the first and second sorbent materials. For purposes herein, the term “distinct” when used in conjunction with the words “flow path” or “migration path” shall be understood to mean “not in fluid communication except via a test zone”.

Where the test cell of the invention is provided in a housing, the housing is provided with a first opening adjacent the first location and a second opening adjacent the second location. A viewing window is provided in the housing above the test line.

In the preferred embodiment of the invention, the first sorbent material and second sorbent material are separate pieces which overlie one another and the test line is printed on one or both of the sorbent materials at the junction. Alternatively, although not preferred, the first and second sorbent materials can be integral with each other. The systems of the invention preferably also include a control line or site which may be seen from the viewing window.

According to one set of embodiments of the invention, the sorbent materials of the invention (and the housing in which the materials are provided) are laid out in a T shape, where the first location for receiving the buffer or buffer-conjugate solution is located near one end of the top bar of the T, the second location for receiving the sample is located near the end of the stem of the T, and the sorbent materials overlie each other at the intersection. According to another set of embodiments of the invention, the sorbent materials of the invention (and the housing in which the materials are provided) take a+shape, where the first location for receiving the buffer or buffer-conjugate solution is located near one end of a first bar, the second location for receiving the sample is located near the end of one end of the second bar, and the sorbent materials overlie each other at the intersection. Of course, the sorbent materials may be laid out in other configurations, and the housing may take other shapes, such as rectangular, square, irregular, etc. regardless of the manner in which the sorbent materials are arranged.

In one embodiment of the invention, the materials, thicknesses and lengths of the first and second sorbent materials are chosen to adjust the timing regarding the liquid sample and liquid buffer reaching the test site.

In the dry conjugate system of the invention, a dry conjugate is provided between the first opening and the test site. The conjugate is supported on or within the sorbent material such that when a buffer is added in the first opening, the sorbent material wicks the buffer to the conjugate which is then carried by the buffer to the test site. In the liquid conjugate system of the invention, a buffer-conjugate liquid subsystem is provided and applied to the first opening. The sorbent material then wicks the buffer-conjugate subsystem to the test site.

According to one method of the invention, a system is provided which includes a test cell having a first sorbent material having a first location for receiving a buffer solution (in the case of a dry conjugate system) or a conjugate solution (in the case of a liquid conjugate system) with the first sorbent material defining a first horizontal flow path, a second sorbent material having a second location for receiving a sample with the second sorbent material defining a second horizontal flow path distinct from the first flow path, and a test line or test site with immobilized antigens or antibodies or other ligand binding molecules such as aptamers, nucleic acids, etc. located in a test zone at a junction of the first and second sorbent materials. If desired, a housing is also provided having a first opening for receiving the buffer or conjugate solution, a second opening for receiving a sample, and a viewing window above the test line. A sample of interest is provided to the second opening or location. After a desired amount of time, a liquid such as a buffer solution is added to the first opening or location. If the sorbent material is supporting a conjugate (i.e., in a dry conjugate system), the liquid is preferably simply a buffer solution. If the sorbent material is not supporting a conjugate (i.e., in a liquid conjugate system), the liquid is preferably a buffer-conjugate liquid subsystem. In any event, after sufficient time to permit the conjugate to migrate to the test site (and control site if provided), the test site (and control site if provided) is inspected in order to determine whether the sample is “positive” or not.

It will be appreciated that the system of the invention can be used in conjunction with different types of samples such as blood, urine, saliva, and feces, and can be used to test for the presence of any ligand. Where blood, saliva or feces is to be provided, the blood, saliva or feces may be diluted or mixed with buffer prior to being added through the second hole. Alternatively, in some cases, the sample may be added through the hole and then a diluent may be added through the same hole.

The test cell of the invention is advantageous over the prior art because the test cell of the invention overcomes aggregation/agglutination problems between the conjugate and the analyte in the sample which is a significant problem in traditional chromatographic immunoassay for relatively large analytes such as bacteria. In particular, in traditional chromatographic immunoassays, the complex between bacteria and conjugated antibody has difficulty migrating to the test line and tends to remain in the bottom of test strip or in the pad. In this invention there is no complex binding between analyte and the conjugate until the sample reaches the test site, as the analyte is applied via its own path to the test site while the conjugate migrates by itself. As a result, the system of the invention is extremely sensitive and specific.

Additional objects and advantages of the invention will become apparent to those skilled in the art upon reference to the detailed description taken in conjunction with the provided figures.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a top schematic view of a first embodiment of the invention.

FIG. 1A is a cross-sectional view taken along line 1A—1A of FIG. 1.

FIG. 1B is a cross-sectional view taken along line 1B—1B of FIG. 1.

FIG. 2 is a top schematic view of a second embodiment of the invention.

FIG. 2A is a cross-sectional view taken along line 2A—2A of FIG. 2.

FIG. 3 is a cross-sectional view of a third embodiment of the invention.

FIG. 4 is a top schematic view of a fourth embodiment of the invention.

FIG. 5 is a top schematic view of a fifth embodiment of the invention.

FIG. 6 is a top schematic view of a sixth embodiment of the invention.

FIG. 7 is a top schematic view of a seventh embodiment of the invention.

FIG. 8 is a top schematic view of an eighth embodiment of the invention.

FIG. 9 is a top schematic view of a ninth embodiment of the invention.

FIG. 10 is a top schematic view of an implementation of the invention which does not use a housing.

FIG. 11 is a table showing a comparison of the sensitivity of the test device of the invention relative to a typical prior art TB test device.

FIG. 12 includes two tables and a key, with the tables showing comparisons of the sensitivity of the test device of the invention relative to typical prior art HIV1 and HIV2 test devices.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Turning now to FIGS. 1, 1A and 1B. an immunoassay device test cell 10 is provided and includes: a T-shaped housing 20 having a top wall 21 defining first and second holes 24, 26, and a window 28; and first and second sorbent or bibulous materials 30, 32 defining perpendicular horizontal flow paths in the housing. The first sorbent material 30 includes at least two and preferably three or four zones and may be made from a plurality of materials. A first zone 31 (sometimes called a filter zone) is located at the first hole 24 and extends to a second zone 33 (sometimes called a test zone) which is located at the junction of the “T”. The first zone 31 preferably includes a filter 31 a, a pad 31b on or in which a conjugate 39 having desired antigens or antibodies with attached colored markers is deposited and immobilized, and a first portion of a thin membrane or sorbent or bibulous material 30 typically made from nitrocellulose with a plastic backing (not shown). The first zone 31 is adapted to receive a buffer solution, to cause the buffer solution to contact the conjugate, thereby mobilizing the conjugate, and to wick the conjugate-carrying buffer solution to the second zone 33. The second (test) zone 33 includes a second portion of the thin membrane 30 which is preferably printed with a test line 50 having immobilized antigens or antibodies (depending on whether the test cell is designed to test for the presence of antibodies or antigens) on the membrane as is well known in the art. The test line 50 may be seen through the window 28 of clear plastic provided in the housing. An optional third zone 35 (sometimes called a control zone) which includes a third portion of the thin membrane 30 may also be printed with a control line 60 typically containing antibodies to the conjugate antigens (or in some cases antibodies which will bind to conjugate antibodies, or even antigens which will bind to conjugate antibodies) as is well known in the art. Where the third zone 35 is provided, window 28 extends above the control line 60. If desired, an optional fourth zone 37 (sometimes called a reservoir zone) may be provided as a wicking reservoir as is also well known in the art. The fourth zone 37 includes a relatively thicker absorbent paper 3d. Preferably overlying all the zones is a thin, preferably transparent plastic film or card 38a having an adhesive which keeps the sorbent materials in place. The card 38 may be cut with an opening at hole 24 so that it does not block liquid access to the hole 24.

The second sorbent material 32 may also be made from a plurality of materials and preferably includes two zones 61, 63. The first zone 61 (sometimes called a filter zone) includes a filter or pad 62 and a first portion of a thin membrane or sorbent or bibulous material 32 typically made from nitrocellulose with a backing (not shown). The first zone 61 is located at the second hole 26 and extends to the second zone 63. The second zone 63 includes a second portion of the thin membrane 32 which is in contact with the second zone 33 of the first sorbent material 30. As is seen in FIGS. 1A and 1B, the first sorbent material 30 overlies the second sorbent material 32 such that the membranes are in contact with each other (as opposed to the backings contacting the membranes or each other), and such that the test line 50 is effectively located between the membranes. Thus, test line 50 could be printed on the second zone 63 of the second sorbent material 32 instead of, or in addition to the second zone 33 of the first sorbent material 30. If desired, a thin plastic film or card 38b having an adhesive which keeps the second sorbent material in place may be utilized.

Where standard-type nitrocellulose strips with a backing are utilized as the first and second membranes, it is desirable for the membranes to have different pore sizes. For example, and as discussed in more detail hereinafter, if membrane 31 (for the conjugate migration) has a 3μ pore size, and membrane 32 (for the sample migration) has a 15μ pore size, sample applied to membrane 32 will tend to migrate and stay in the sample membrane 32 and will tend not to migrate into the conjugate membrane 31.

The immunoassay of FIG. 1 is preferably utilized as follows. First, a sample (not shown) possibly containing antibodies (or antigens) is provided to the second opening or hole 26 and allowed to migrate through the second sorbent material 32 to its second zone 63 which is contact with the second zone 33 of the first sorbent material 30. Optionally, after providing the sample to hole 26, a preferably measured amount of liquid such as a buffer solution may be added to hole 26 to help in the migration of the sample. Regardless, the sample reaches the test line 50 which is printed atop the second zone 33 of the first sorbent material or infused therein. After a desired amount of time, by which time the antibodies (or antigens) in the sample (if present) will have had an opportunity to bind to the antigens (or antibodies) immobilized at the test line 50, a preferably measured amount of liquid such as a buffer solution (not shown) is added to the first opening 24. After another period of time, sufficient to permit the conjugate to migrate to the test site 50 (and control site 60 if provided), the test site 50 (and control site 60 if provided) is inspected via window 28 in order to determine whether the sample is “positive” or not. Typically, a “positive” test indicating the presence of the antibody (or antigen) in the sample is obtained when both the test site 50 and the control site 60 show lines of color. A “negative” test indicating the lack of the presence of the antibody (or antigen) in the sample is obtained when only the control site 60 shows a line of color.

The method of the invention may be expedited by providing the housing with numbering and/or lettering to indicate that hole 26 is for receiving the sample (and optionally some buffer) and is to be used first, and that hole 24 is for receiving the buffer solution and is to be used second.

Those skilled in the art will appreciate that the immunoassay 10 functions as follows. Because the test line 50 is provided with antigens (or antibodies) immobilized on a membrane, if the test sample contains antibodies to the antigens (or antigens to the antibodies), the antibodies (or antigens) will bind themselves to the antigens (or antibodies) at the test line. Thereafter, when the conjugate 39 containing an antigen for the antibody (or antibody for the antigen) coupled to a colored marker is caused to migrate to the test line, if the test sample contains the antibodies (or antigens) which are now held at the test line 50, the antigen (or antibody) of the conjugate will bind itself to the antibodies (or antigens) and the colored marker will cause a colored line to appear at the test site 50. If the test sample does not contain antibodies (or antigens), the conjugate will not have the antibodies (antigens) to bind to at the test line 50, and no colored line will appear at the test site 50. On the other hand, because the control line 60 is provided with antibodies (or antigens), the antigens (or antibodies) of the conjugate will always bind to the antibodies (or antigens) in the control line 60, thereby causing a colored line to appear at the control site 60 if the conjugate reaches the control site 60. Thus, if sufficient buffer solution is provided to the test cell, a colored line should always appear at the control site 60, thereby providing a control for the test.

Turning now to FIG. 2 and FIG. 2A, a second embodiment of the invention is seen. In FIGS. 1, 1A, 1B, 2 and 2A, like numbers are used for like elements. Thus, it will be appreciated that the primary difference between the second embodiment of FIGS. 2 and 2A and the first embodiment of FIGS. 1, 1A, and 1B is that the second sorbent material 32a of test cell 10a is key-shaped (preferably via punching). With the key-shaped arrangement, zone 61a is shaped so that it converges to the second narrow zone 63a. As a result, zone 63a touches the second zone 33 of the first sorbent material 30 almost exclusively at the location of the test line 50. Those skilled in the art will appreciate that the immunoassay test cell 10a of FIG. 2 may be used in the same manner and functions substantially the same as the test cell 10 of FIG. 1.

Turning now to FIG. 3, a third embodiment of the invention is seen. In FIGS. 1, 1A, 1B and 3, like numbers are used for like elements. Thus, it will be appreciated that the primary difference between test cell 10b of the third embodiment of FIG. 3 and test cell 10 of the first embodiment of FIGS. 1, 1A, and 1B is that overlying the second nitrocellulose strip 32 at the location where the first nitrocellulose strip 30 contacts the second strip (except for a narrow zone at and adjacent test site 50) is a very thin layer of non-porous material 99 such as plastic. As a result of material 99, the strips 30 and 32 contact each other almost exclusively at the location of the test line 50. Those skilled in the art will appreciate that the immunoassay test cell 10b of FIG. 3 may be used in the same manner and functions substantially the same as the test cell 10 of FIG. 1.

Turning now to FIG. 4, a fourth embodiment of the immunoassay device is shown with a test cell 10′ (slightly modified relative to test cell 10 of FIG. 1) provided which includes: a T-shaped housing 20′ having a top wall 21′ defining first and second holes 24′, 26′, and a window 28′; and first and second sorbent or bibulous materials 30′, 32′ defining perpendicular horizontal flow paths in the housing. The first sorbent material 30′ includes at least two and preferably three or four zones and may be made from a plurality of materials. A first zone 31′ (sometimes called a filter zone) is located at the first hole 24′ and extends to a second zone 33′ (sometimes called a test zone) which is located at the junction of the “T”. The first zone 31′ preferably includes a filter, a pad on or in which a conjugate 39′ having desired antigens or antibodies with attached colored markers is deposited and immobilized, and a thin membrane typically made from nitrocellulose (which extends to the second and optional third and fourth zones) with a backing. The first zone 31′ is adapted to receive a buffer solution, to cause the buffer solution to contact the conjugate, thereby mobilizing the conjugate, and to wick the conjugate-carrying buffer solution to the second zone 33′. The second zone 33′ has printed thereon a test line 50′ which, as discussed hereinafter is located under the second sorbent material 32′. An optional third zone 35′ (sometimes called a control zone) may be provided with a control line 60′ typically containing antibodies to the conjugate antigens (or in some cases antibodies which will bind to conjugate antibodies, or even antigens which will bind to conjugate antibodies) as is well known in the art. Where the third zone 35′ is provided, window 28′ extends above the control line 60′. If desired, an optional fourth zone 37′ (sometimes called a reservoir zone) may be provided as a wicking reservoir as is also well known in the art. The fourth zone 37′ includes a relatively thicker absorbent paper. Preferably underlying all four zones is a thin plastic film having an adhesive which keeps the sorbent materials in place.

The second sorbent material 32′ may also be made from a plurality of materials and preferably includes two zones 61′, 63′. The first zone 61′ (sometimes called a filter zone) is located at the second hole 26′ and extends to the second zone 63′ which is in contact with the second zone 33′ of the first sorbent material 30′. If desired, the second zone 63′ of the second sorbent material 32′ may be printed with the test line 50′ having immobilized antigens or antibodies (depending on whether the test cell is designed to test for the presence of antibodies or antigens) as is well known in the art. Regardless of whether second zone 63′ or second zone 33′ or both are provided with the test line 50′, the test line 50′ may be seen through the window 28′ of clear plastic provided in the housing. As is suggested by the lines in FIG. 4 (compare FIG. 1), the second sorbent material 32′ overlies the first sorbent material 30′, such that the thin membranes of both materials are in contact with each other at least at the test line location. The second sorbent material 32′ may be shaped as in FIG. 1 so that a standard nitrocellulose strip with backing is provided. Alternatively, material 32′ may be shaped as in FIG. 2 such that it touches the first sorbent material almost exclusively at the location of the test line 50′. As another alternative, the material 32′ may be shaped as in FIG. 1, and a thin non-porous membrane can be provided as in FIG. 3 such that materials 30′ and 32′ touch each other almost exclusively at the location of the test line 50′.

Those skilled in the art will appreciate that the immunoassay test cell 10′ of FIG. 4 may be used in the same manner and functions substantially the same as the test cell 10 of FIG. 1.

Turning now to FIG. 5, an immunoassay device test cell 10″ is provided and includes: a T-shaped housing 20″ having a top wall 21″ defining first and second holes 24″, 26″, and a window 28″; and a T-shaped sorbent or bibulous material 30″ defining perpendicular flow paths in the housing. The T-shaped sorbent material 30″ includes at least three and preferably four or five zones and may be made from a plurality of materials. A first zone 31″ (sometimes called a filter zone) is located at the first hole 24″ and extends to a second zone 33″ (sometimes called a test zone) which is located at the junction of the “T”. The first zone 31″ preferably includes a filter, a pad on or in which a conjugate 39″ having desired antigens or antibodies with attached colored markers is deposited and immobilized, and a thin membrane typically made from nitrocellulose and a backing therefor. The first zone 31″ is adapted to receive a buffer solution, to cause the buffer solution to contact the conjugate, thereby mobilizing the conjugate, and to wick the conjugate-carrying buffer solution to the second zone 33″. The second (test) zone 33″ is preferably printed with a test line 50″ having immobilized antigens or antibodies (depending on whether the test cell is designed to test for the presence of antibodies or antigens) on the membrane as is well known in the art. The test line 50″ may be seen through the window 28″ of clear plastic provided in the housing. The third zone 61″ (sometimes also called a filter zone) is located at the second hole 26″, is perpendicular to the strip defined by the first and second zones, and extends to the second zone 33″. An optional fourth zone 35″ (sometimes called a control zone) may also be printed with a control line 60″ typically containing antibodies to the conjugate antigens (or in some cases antibodies which will bind to conjugate antibodies, or even antigens which will bind to conjugate antibodies) as is well known in the art. Where the fourth zone 35″ is provided, window 28″ extends above the control line 60″. If desired, an optional fifth zone 37″ (sometimes called a reservoir zone) may be provided as a wicking reservoir as is also well known in the art. The fifth zone 37″ includes a relatively thicker absorbent paper. Preferably underlying all of the zones is a thin plastic film having an adhesive which keeps the sorbent materials in place.

The embodiment of FIG. 5 differs from the embodiments of FIGS. 1–4 only in that instead of using two separate strips of material which overlie each other at the test zone, a single T-shaped membrane is utilized which defines a first horizontal strip with zones 31″, 33″ and preferably 35″ and 37″, and a second (integral) strip with zone 61″ which touches the first strip at test zone 33″. While the embodiment of FIG. 5 does not permit the horizontal flow paths to be tailored with materials of different pore sizes, two distinct migration paths are maintained as the first and third zones are not in fluid communication with each other except via the second (test) zone.

Turning now to FIG. 6, an immunoassay device test cell 110 is provided and includes: a +-shaped housing 120 having a top wall 121 defining first and second holes 124, 126, and a window 128; and first and second sorbent or bibulous materials 130, 132 defining perpendicular flow paths in the housing. The first sorbent material 130 includes at least two and preferably three or four zones and may be made from a plurality of materials. A first zone 131 (sometimes called a filter zone) is located at the first hole 124 and extends to a second zone 133 (sometimes called a test zone) which is located at the junction of the “+”. The first zone 131 preferably includes a filter, a pad on or in which a conjugate 139 having desired antigens or antibodies with attached colored markers is deposited and immobilized, and a thin membrane typically made from nitrocellulose. The first zone 131 is adapted to receive a buffer solution, to cause the buffer solution to contact the conjugate, thereby mobilizing the conjugate, and to wick the conjugate-carrying buffer solution to the second zone 133. The second (test) zone 133 is preferably printed with a test line 150 having immobilized antigens or antibodies (depending on whether the test cell is designed to test for the presence of antibodies or antigens) on the membrane as is well known in the art. The test line 150 may be seen through the window 128 of clear plastic provided in the housing. An optional third zone 135 (sometimes called a control zone) may also be printed with a control line 160 typically containing antibodies to the conjugate antigens (or in some cases antibodies which will bind to conjugate antibodies, or even antigens which will bind to conjugate antibodies) as is well known in the art. Where the third zone 135 is provided, window 128 extends above the control line 160. If desired, an optional fourth zone 137 (sometimes called a reservoir zone) may be provided as a wicking reservoir as is also well known in the art. The fourth zone 137 includes a relatively thicker absorbent paper. Preferably overlying the zones (in a manner such as seen in FIG. 1A) is a thin plastic film having an adhesive which keeps the sorbent materials in place.

The second sorbent material 132 may also be made from a plurality of materials and preferably includes at least three zones 161, 163, 165. The first zone 161 (sometimes called a filter zone) is located at the second hole 126 and extends to the second zone 163 which is in contact with the second zone 133 of the first sorbent material 130. If desired, the sorbent material 132 may be printed with the test line 150 at the second zone 163 instead of or in addition to second zone 133 of material 130. As is suggested by the dotted lines in FIG. 6, the first sorbent material 130 overlies the second sorbent material 132 (as in the embodiment of FIG. 1). Alternatively, the second sorbent material 132 can be made to overlie the first sorbent material 130 (as in the embodiment of FIG. 4), in which case the adhesive films where utilized, and other elements should be properly arranged. If desired, an optional third zone 165 (sometimes called a reservoir zone) may be provided as a wicking reservoir. The fourth zone 137 includes a relatively thicker absorbent paper. If desired, a thin plastic film having an adhesive which keeps the second sorbent material in place may be utilized.

In FIG. 7, a seventh embodiment of the invention is seen. In FIGS. 1, 1A, 1B and 7, like numbers are used for like elements. Thus, it will be appreciated that the primary difference between the seventh embodiment of FIG. 7 and the first embodiment of FIGS. 1, 1A, and 1B is that two test lines 50A and 50B are printed on zone 33 of first sorbent material 30 and/or on zone 63 of second sorbent material 32. The two test lines 50A and 50B preferably include different immobilized antigens or antibodies. For example, one of the lines (e.g., line 50A) could include HIV1 peptides and/or recombinant antigens such as gp41/gp120, while the other line (e.g., line 50B) could include HIV2 peptides and/or recombinant antigens such as gp36. As another example, one of the lines could include HIV1, HIV2, or HIV1/2 peptides and/or recombinant antigens, while the other line includes tuberculosis antigens. As discussed below, where the test lines include immobilized antibodies or antigens that will not bind to a single conjugate (such as Protein A), it may be desirable to use a plurality of different conjugates having desired antigens or antibodies with attached colored markers. Those skilled in the art will appreciate that the immunoassay test cell 10c of FIG. 7 may be used in the same manner and functions substantially the same as the test cell 10 of FIG. 1, except that a “positive” test indicating the presence of a first antibody (or antigen) being tested in the sample is obtained when test line 50A and the control site 60 show lines of color; a “positive” test indicating the presence of a second antibody (or antigen) being tested in the sample is obtained when test line 50B and the control site 60 show lines of color; and a “positive” test indicating the presence of both the first and second antibodies (or antigens) being tested in the sample is obtained when test lines 50A and 50B and the control site 60 show lines of color. A “negative” test indicating the lack of the presence of the antibody (or antigen) in the sample is obtained when only the control site 60 (and neither of test lines 50A and 50B) shows a line of color. An invalid test is obtained when the control site does not show a line of color.

In FIG. 8, an eighth embodiment of the invention is seen. In FIGS. 1, 1A,1B and 8, like numbers are used for like elements. Thus, it will be appreciated that the primary differences between the eighth embodiment of FIG. 8 and the first embodiment of FIGS. 1, 1A, and 1B is that three test lines 50A, 50B, 50C are printed on zone 33 of first sorbent material 30 and/or on zone 63 of second sorbent material 32, and that two different latex conjugates 39A, 39B are utilized. The three test lines 50A, 50B, and 50C preferably include different immobilized antigens or antibodies. For example, one of the lines (e.g., line 50A) could include p24 monoclonal antibodies, a second line (e.g., line 50B) could include HIV1 peptides and/or recombinant antigens such as gp41/gp120, while the third line (e.g., line 50C) could include HIV2 peptides and/or recombinant antigens such as gp36. In this case, two conjugates 39A, 39B are provided, with conjugate 39A being a latex conjugate with protein A which will bind to HIV1 and HIV2 antibodies, if present, but will not bind to the p24 antigen, and conjugate 39B being a latex conjugated to p24 monoclonal which will bind to the p24 antigen in the sample, if present, but will not bind to the HIV1 and HIV2 peptides and/or recombinant antigens. As shown in FIG. 8, the conjugates 39A and 39B are located at different locations of the migration path (e.g., on two portions of a single pad, or on two connected pads). However, it will be appreciated that the conjugates 39A and 39B may be applied to the same location as a mixture. Those skilled in the art will appreciate that the immunoassay test cell 10d of FIG. 8 may be used in the same manner and functions substantially the same as the test cell 10 of FIG. 1, except that a “positive” test for HIV is indicated by the visibility of color at one or more of lines 50A, 50B, 50C, and at control line 60, a “negative” test is indicated by the visibility of color at control line 60 only, and an “invalid” test is indicated when no color appears at control line 60.

A ninth embodiment of the invention is seen in FIG. 9. In FIGS. 1, 1A, 1B and 9, like numbers are used for like elements. Thus, it will be appreciated that the primary difference between the ninth embodiment of FIG. 9 and the first embodiment of FIGS. 1, 1A, and 1B is that the second sorbent material 32″′ includes a first zone 61″′ (sometimes called a filter zone) having a filter or pad 62″′ which has thereon a conjugate 39″′ of an antibody bound to an interim binding agent (without marker), and the test zone has a test line 50 of an immobilized binding agent. The interim binding agent and immobilized binding agent are chosen for their ability to selectively bind extremely well to each other. Thus, for example, the interim binding agent may be biotin and the immobilized binding agent may be streptavidin. The conjugate 39″′ in the sample migration path may therefore be an antibody such as a p24 monoclonal antibody which is bound to biotin. Likewise, the conjugate 39 in the buffer migration path is preferably a latex marker conjugate with an antibody (e.g., a monoclonal antibody) which will bind to the antigen of interest.

With the test cell 10e of FIG. 9 which is arranged to detect a p24 virus, a sample is first added to the second sorbent material 32″′. When the sample reaches the p24 monoclonal antibody—biotin conjugate 39″′, the p24 antigen (virus), if present in the sample, will bind with the p24 monoclonal antibody—biotin conjugate, and will migrate to the test area 63″′ of strip 32″′ where the biotin will be captured by the streptavidin at the test line 50 located on strip